TERN-601
TERN-601, oral small-molecule GLP-1 receptor agonist
Written by Aaron CuhaReviewed Sep 2026
Also known as: Terns oral GLP-1
Dose-dependent weight loss in phase 1 and phase 2, then discontinued after three participants developed liver enzyme elevations consistent with potential drug-induced liver injury.
Overview
The second oral small-molecule GLP-1 agonist in this batch to work and be stopped, and its report is unusually clear about why.
Phase 1 ran 28 days and produced dose-dependent weight loss with statistically significant reductions against placebo at every dose, along with the pharmacodynamic signatures you would expect from this class: reduced appetite and delayed gastric emptying. Phase 2 ran 12 weeks and found significantly greater weight loss at doses of 500 mg and above.
Then three participants in the phase 2 study experienced transaminase elevations consistent with potential drug-induced liver injury, and clinical development was discontinued.
The authors' own framing is worth repeating: modest dose-dependent weight loss with gastrointestinal tolerability consistent with the class, and liver safety findings that ended the programme. Publishing that is more useful than quietly shelving it.
Mechanism of action
An orally administered small-molecule agonist at the GLP-1 receptor, dosed once daily. Small molecules bind the receptor differently from the native peptide because they cannot reproduce its large binding surface, but the downstream signalling is the same: glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying and reduced appetite. Confirmed in this programme by measured reductions in appetite and delayed gastric emptying alongside weight loss.
Human evidence
Phase 1 and phase 2 published together, both randomised and placebo-controlled, showing efficacy and the liver finding that ended the programme.
- Phase 1, 28 days: dose-dependent weight loss with statistically significant reductions against placebo at all doses.
- Measured pharmacodynamics consistent with the class: reduced appetite and delayed gastric emptying.
- Phase 2, 12 weeks: significantly greater weight loss at 500 mg and above against placebo.
- Gastrointestinal adverse events were class-consistent and dose-related.
- Three phase 2 participants developed transaminase elevations consistent with potential drug-induced liver injury.
- Those findings led directly to discontinuation of clinical development, which the authors state plainly.
What this does not tell you: The efficacy is described by its own authors as modest, and the phase 2 was 12 weeks, which is short for a weight outcome in this class where the comparators run 68 to 72 weeks. Three liver events is a small number and it was enough to stop a programme, which tells you how seriously that signal is taken rather than how common it is. Nothing here establishes what the risk would have been at scale, because the programme ended before anyone found out.
Reading the research record
Read the oral small-molecule GLP-1 agonists as a group and one thing stands out. Efficacy was not the obstacle. Lotiglipron cut HbA1c by up to 1.44 percent and produced up to 7.47 percent weight loss against 1.84 percent on placebo in 901 participants, and its trial was terminated early for safety. TERN-601 produced statistically significant dose-dependent weight loss at every dose in phase 1 and significant weight loss at 500 mg and above in phase 2, and was discontinued after three participants developed transaminase elevations consistent with potential drug-induced liver injury. Orforglipron reached approval. Two of three credible programmes were stopped by the liver rather than by a lack of effect, which is a class-level consideration: an orally absorbed small molecule reaches the liver first and at the highest concentration it will encounter anywhere. That does not make every oral agent in this class dangerous, and it does mean liver monitoring is a specific and non-theoretical part of the story rather than boilerplate.
The evidence, charted
Fig. 1 · evidence composition
2of 2 citations (100%) are in people
Every citation cited here is Human work; no other study type is cited on this page. This count is of our own citation list and understates any literature larger than the sources we cite.
Fig. 2 · evidence over time
Citations here span just two years, 2025 and 2026.
Too few distinct publication years on this page to plot as a timeline.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Not approved
CA
Not approved
Approved in 1 of 4, prescription route in 0, not approved in 3. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2026
Oral GLP-1RA TERN-601 for adults with obesity or overweight: placebo-controlled, multiple-ascending-dose, phase 1 and 2 studies
Phase 1 over 28 days and phase 2 over 12 weeks, both randomised, double-blind and placebo-controlled. Phase 1 produced dose-dependent weight loss with statistically significant reductions against placebo at all doses, plus reduced appetite and delayed gastric emptying. Phase 2 produced significantly greater mean percentage weight loss at doses of 500 mg and above at week 12. Gastrointestinal adverse events were class-consistent and dose-related. Three participants in phase 2 experienced transaminase elevations consistent with potential drug-induced liver injury, and those liver safety findings led to discontinuation of clinical development.
Obesity - Human2025
Evaluation of an oral small-molecule glucagon-like peptide-1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: a dose-ranging study
The other half of the pattern. A separate oral small-molecule GLP-1 agonist, efficacious in 901 participants, whose phase 2 was terminated early for safety. Two independent programmes in the same class stopped for safety rather than for lack of effect.
Diabetes, Obesity and Metabolism
Frequently asked questions
What happened to TERN-601?
It worked and it was stopped. Dose-dependent weight loss in phase 1 at every dose and significant weight loss at 500 mg and above in phase 2, then three participants developed liver enzyme elevations consistent with potential drug-induced liver injury and clinical development was discontinued.
Three people is not many. Why stop?
Because drug-induced liver injury is the reason more drugs are withdrawn after approval than almost any other cause, and a signal in a few hundred participants implies something quite different at a population scale. Stopping early is the correct response to that signal, and it also means nobody found out what the real rate would have been.
Is an oral GLP-1 pill a bad idea then?
No. Orforglipron was approved, so the concept works. What these two programmes establish is that the liver is the organ to watch for this class, which follows from the pharmacology: an orally absorbed small molecule reaches the liver first and at the highest concentration it encounters anywhere in the body.